Sarcoidosis

Per-Johan Jakobsson, Ernesto Silva , Bettina Levänen, Hanna Eriksson Divison of Respiratory Medicine: Johan Grunewald, Anders Eklund

Prof. Lee Newman, Department of Preventive Medicine and Biometrics, University of Colorado at Denver, USA

Sarcoidosis is a granulomatous disease of unknown etiology, with approximately 2000 new cases in Sweden yearly. The disease primarily affects young adults (age 25-40). Although sarcoidosis is a systemic disease, it most commonly affects the lungs. The majority of patients recover, but some develop a chronic inflammatory lung disease which results in fibrosis and eventually respiratory failure, with a mortality rate of about 5%. Chronic Beryllium Disease (CBD) is a granulomatous disease that occurs in individuals exposed to beryllium, primarily at their workplaces. CBD resembles sarcoidosis both clinically and immunologically. In both diseases, certain polymorphisms in the HLA molecule have been shown to cause a genetic predisposition for a more severe manifestation of the disease. In this project, we are using proteomics applications to identify specific biomarkers of disease, as well as to elucidate the mechanisms underlying the varying disease progression. Initial proteomics analyses of bronchoalveolar lavage (BAL) fluid using gel-based approaches resulted in identification of several putative biomarkers for CBD as well as for sarcoidosis. In addition, potential biomarkers for distinguishing between the two conditions were discovered. The next step will be to study intracellular proteins in certain BAL cell subsets such as alveolar macrophages and CD4+ T cells to reveal the distinct alterations in protein expression of these cell types in relation to acute and chronic disease. Based on recent data indicate the presence of Mycobacteria-derived antigens in sarcoidosis patients, an additional goal of these studies is to identify exogenous antigens derived from Mycobacteria or other pathogens in BAL cells of these patients. To this end, analysis of membrane proteins will be performed in close collaboration with Per-Johan Jacobsson, who has extensive experience in the field of membrane proteomics.

Last updated: 2008-11-10